What is the role of Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors in patients with End-Stage Renal Disease (ESRD) on dialysis?

From the Guidelines

SGLT2 inhibitors are not recommended for patients with End-Stage Renal Disease (ESRD) on dialysis due to limited evidence of their effectiveness and potential safety concerns. The KDOQI Work Group believes that there is not enough evidence to suggest that these medications are effective in patients receiving kidney replacement therapy 1. Although some limited data suggests that dapagliflozin may be safe to use in persons receiving dialysis, the US Food and Drug Administration (FDA) has only concluded that there were no safety signals based on the DAPA-CKD trial 1.

The mechanism of action of SGLT2 inhibitors, which involves preventing glucose reabsorption in the proximal tubule of the kidney, becomes ineffective in dialysis patients who have minimal to no kidney function and often produce little to no urine. The glycemic benefits of these medications are therefore largely absent in this population. Additionally, there are safety concerns including volume depletion and potential for hypotension, particularly during dialysis sessions.

Some ongoing trials are exploring the potential benefits of SGLT2 inhibitors in dialysis and transplant patients, but until more evidence is available, other antidiabetic medications like insulin, certain GLP-1 receptor agonists, or DPP-4 inhibitors would be more appropriate choices for glycemic control in dialysis patients, as they don't rely on kidney function for their mechanism of action. Key considerations for medication management in dialysis patients include:

• Consulting with a nephrologist before making medication changes
• Prioritizing medications with established benefits and safety profiles in this population
• Carefully monitoring patients for potential adverse effects, particularly volume depletion and hypotension.

From the FDA Drug Label

Efficacy and safety trials with INVOKANA did not enroll adult patients with ESKD on dialysis or patients with an eGFR less than 30 mL/min/1.73 m 2 Canagliflozin was negligibly removed during a 4-hour hemodialysis session. DAPAGLIFLOZIN TABLETS are likely to be ineffective in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1. 73 m2 based upon its mechanism of action.

The role of Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors, such as canagliflozin and dapagliflozin, in patients with End-Stage Renal Disease (ESRD) on dialysis is not established due to lack of enrollment in efficacy and safety trials 2 3. Additionally, SGLT2 inhibitors are likely to be ineffective in this population based on their mechanism of action, which relies on adequate renal function to increase urinary glucose excretion. Caution should be exercised when considering the use of SGLT2 inhibitors in patients with ESRD on dialysis.

From the Research

Role of SGLT2 Inhibitors in Patients with End-Stage Renal Disease (ESRD) on Dialysis

• The use of Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors in patients with End-Stage Renal Disease (ESRD) on dialysis is a topic of interest, with limited reports available on their use in this population 4.
• SGLT2 inhibitors have been shown to reduce glycated hemoglobin (A1C), weight, and blood pressure, which can help slow the progression of renal disease by impacting the underlying mechanisms of kidney injury 5.
• In patients with type 2 diabetes and preserved kidney function, SGLT2 inhibitors have been shown to improve glycemic control, reduce body weight and body fat, and have a low risk of causing hypoglycemia 6.
• A follow-up study on chronic peritoneal dialysis patients found that SGLT2 inhibitors may increase ultrafiltration volume and hemoglobin levels, but did not increase urinary tract infection, and was linked to subclinical metabolic acidosis 4.
• The effect of SGLT2 inhibitors in chronic peritoneal dialysis patients is not entirely clear, but they may be associated with increased ultrafiltration, hemoglobin, white blood cell counts, and a decreased CO2 in PD patients 4.

Mechanism of Action

• SGLT2 inhibitors work by inhibiting the sodium-glucose cotransporter 2 channel (SGLT2) in the proximal tubules of the kidney, reducing sodium and glucose reabsorption and increasing urinary glucose excretion 7, 8.
• This mechanism of action can help improve glycemic control, reduce hyperglycemia, and slow the progression of renal disease 6, 5.

Clinical Implications

• SGLT2 inhibitors may be a useful therapeutic option for patients with ESRD on dialysis, particularly those with type 2 diabetes, to improve glycemic control and reduce the risk of cardiovascular complications 7, 5.
• However, caution is advised when prescribing SGLT2 inhibitors to patients with moderately impaired renal function and those at risk for volume depletion and hypotension 5.